Quaternary salts of basic esters of beta-(1-naphthyl)-acrylic acid



United States Patent 3,420,822 QUATERNARY SALTS 0F BASIC ESTERS 0Ffi-(l-NAPHTHYD-ACRYLIC ACID Silvano Casadio, Milan, Italy, assignor toIstituto de Angeli S.p.A., Milan, Italy, an Italian body corporate NoDrawing. Filed Oct. 20, 1965, Ser. No. 499,014 Claims priority,application Italy, Nov. 2, 1964, 44,572 US. Cl. 260240 Claims Int. Cl.C091) 23/00; C09b 55/00; C07c 69/76 ABSTRACT OF THE DISCLOSURE Thisinvention relates to quaternary salts of basic esters offl-(l-naphthyD-acrylic acid having valuable antibacterial and antifungalactivities. The quaternary salts of the invention possess the generalformula wherein R is hydrogen or phenyl, R and R individually representmethyl or ethyl or when taken collectively with the nitrogen atom towhich they are attached represent morpholino, piperidino or pyrrolidino;R represents methyl, ethyl, butyl, isoamyl, octyl, decyl, dodecyl,hexadecyl, octadecyl, bromohexyl, benzyl or an acetyl and X represents abromide, chloride or iodide ion or a methyl sulfate ion.

According to the present invention, there are provided compounds of thegeneral formula:

in which:

As stated above, the compounds according to the invention have valuableantibacterial and antifungal activities 3,420,822 Patented Jan. 7, 1969ICC and are particularly intended for the topical treatment of bacterialand fungal infections. In compounds of the Formula I in which Rrepresents an aryl group, it preferably represents a phenyl group. WhenR and R represent alkyl groups, they advantageously represent alkylgroups containing from 1 to 6 carbon atoms; where R and R together withthe adjacent nitrogen atom represent a heterocyclic group, this isadvantageously a 5- or 6-membered saturated heterocyclic group such asfor example a pyrrolidino, piperidino or morpholino group. R preferablyrepresents an alkyl group containing from 1 to 20 carbon atoms (e.g. amethyl, ethyl, butyl, isoamyl, octyl, decyl, dodecyl, hexadecyl oroctadecyl group), a bromoalkyl group such as for example a 6-bromo-hexylgroup; a benzyl group; or an acetyl group. X preferably represents achlorine, bromine or iodine atom, or a methyl sulphate group.

Particularly preferred compounds according to the invention by virtue oftheir especially valuable antibacterial and antifungal activities arecompounds of the Formula I in which R represents an alkyl groupcontaining from 8 to 12 carbon atoms such as, for example, thefollowing:

(a) 2- dimethylamino ethyl [3- l-naphthyl) -acrylate dodecyl bromide,

(b 2- (N-pyrrolidino) ethyl )3- l-naphthyl) -acrylate decyl bromide,

(c) 2- (N-morpholino) ethyl p-( 1-naphthyl)-acrylate decyl bromide, and

(d) 1-phenyl-2 (N-piperidino) ethyl fil-naphthyl) acrylate decylbromide.

Of these compounds, compound (b) is particularly preferred for use inmedicinal preparations.

The antibacterial activity of compounds according to the invention maybe demonstrated by in vitro tests utilising the dilution technique (1:2in tryptose phosphate broth [Difco]) against the followingmicroorganisms: Bacillus subtilis ATCC 6633, Micrococcus pyogencs, var.aureus ATCC 6538P, Streptococcus haemolyticus C203 America, Escherichiacoli McLeod ATCC 10536, Proteus vulgaris ATCC 7829 and Pscudomonasaeruginosa ATCC 10145. 18-24 hours old cultures of the microorganisms,suitably diluted, were inoculated with the compounds to be tested and,after incubation for 24 hours at 37 C., the minimum concentration ofcompound which effected in hibition of the growth of the microorganismswas estimated.

The antifungal activity of compounds according to the invention has beendemonstrated by in vitro tests utilising the dilution technique (1:2 inSabourauds medium) against the following microorganisms: Candidaalbicans ATCC 10231. T ricophyton mentagrophytes ATCC 8757 andSaccharomyces cerevisiae ATCC 9763. With Candida albicans andSaccharomyces cerevisiae incubation was offected, after innoculation ofthe compounds to be tested, for a period of 24 hours prior to estimationof the minimum inhibitory concentration; with Tricophytonmentagrophytes, the incubation period was five days.

In the following table, the results of tests carried out on thecompounds (a), (b), (c) and (d) according to the invention aresummarised. These tests were carried out by means of the suspensiontechnique according to the method of Said and coll. described in Annalespharmv franc. 21, 187, 1963, and the results demonstrate thebactericidal and fungicidal activities of the four compounds even atvery low concentrations.

(wherein R R and R are as hereinbefore defined). The reaction isadvantageously carried out in an organic sol- Compounds according to theinvention have also been tested on rabbits eyes and by subcutaneousinjection into the abdomen of mice in order to ascertain the suitabilityof the compounds for topical application. These tests demonstrated thatthe compounds according to the invention have good skin compatibility.

Further according to the invention, there is provided a process for thepreparation of compounds of the Formula I which comprises reacting anamine of the general formula with a quaternising agent to introduce thesubstituent R and the anion X.

The quaternising agent will in general be a compound of the formula RX', where X is a halide or alkyl sulphate ion. Where it is desired thatthe final compound have an anion other than halide or alkyl sulphatethis may be achieved by conventional ion-exchange techniques.

The reaction is conveniently carried out in the presence of an organicsolvent such as, for example, benzene, toluene, acetone or acetonitrile,advantageously at a temperature between and 50 C. The reaction time willgenerally vary between 2 and 60 days according to the nature of thereactants used. The quaternary salts of Formula I are in generalrelatively insoluble in the organic solvent medium and slowlyprecipitate in crystalline form; in some cases, however, it is desirableto remove the solvent in order to isolate the product. The compounds ofFormula I obtained may be purified in any convenient way, for example bywashing with ether.

The compounds of Formula II used as starting materials in theabove-described process according to the invention may be prepared inany convenient manner, e.g. by one of the following methods:

(1) Reaction of the corresponding B-(l-naphthyD- acrylic chloride withan aminoalcohol of formula:

R2 HOCH-CHr-N 1 1 \R3 (IV) (wherein R R and R are as hereinbeforedefined). The reaction is preferably carried out in the presence of anorganic solvent such as for example ether, benzene or dioxan undersubstantially anhydrous conditions and in the presence of anacid-binding agent such as, for example, an excess of the aminoalcoholofFormula IV. The reaction mixture is advantageously refluxed for 24 hoursto effect the reaction.

(2) Reaction of the sodium B-(I-naphthyD-acrylate with a chloroamine offormula:

vent such as for example ethanol or propanol, refluxing the reactionmixture for l5-24 hours.

The compounds of Formula II may be viscous liquids of pale yellow colouror white crystalline solids, insoluble in Water but soluble in thecommon organic solvents and in aqueous acid solutions. Several of thecompounds of Formula II useful as starting materials are now compounds.

The compounds of Formula I according to the inven tion are in generalcolourless crystalline solids having varying solubilities in water. Thequaternary salts formed with benzyl chloride, methyl chloride, butylbromide and isoamyl bromide are for example soluble in Water whilst thesalts formed with longer chain alkyl halides are either insoluble oronly sparingly soluble in water.

Further according to the invention there are provided pharmaceuticalcompositions (and especially compositions adapted for topical use) whichcomprise at least one compound of the Formula I in association with apharmaceutical carrier or excipient. The compositions according to theinvention may for example be suitable for application to the skin, oralternatively may be adapted for use in the nose, ear or mouth. Thecompositions may for example be in the form of ointments, creams, mouthwashes, nasal and otological drop solutions, alcoholic tinctures,powders for topical use, vaginal tablets and suppositories, spraysolutions and the like. Preferred compositions according to theinvention contain from 0.02 to 1.5% by weight of the compound orcompounds of Formula I. If desired, the compositions according to theinvention may also contain :further therapeutic compounds in addition tocompounds of the Formula I, for example anti-inflammatory steroids (e.g.prednisolone, triamcinolone, betamethazone or dexamethasone),antibiotics especially suitable for topical administration (e.g.neomycin) and local anaesthetics (e.g. xylocaine).

In order that the invention may be well understood, the followingexamples are given by way of illustration only:

EXAMPLE 1 19.8 g. of B-(l-naphthyD-acrylic acid and 50 ml. of thionylchloride are refluxed for 1 hour. The excess of thionyl chloride isdistilled off at reduced pressure and the oily residue is redissolved in20 ml. of anhydrous benzene. 14.5 g. of 2-(N-piperidino)-ethanol in 20ml. of anhydrous benzene are then slowly added to the benzene solutionwhich is externally cooled during the addition in order not to allow thetemperature to rise above 20 C. A further 20 ml. of anhydrous benzeneare then added and the reaction mixture is refluxed for 3 hours. Aftercooling, the suspended solid is filtered, washed with benzene andcrystallised from absolute ethanol. The 2- (N-piperidino)-ethylfi-(l-naphthyD-acrylate hydrochloride is thus obtained (M. Pt. 197 C.).

The free base, obtained by treatment of an aqueous solution of thehydrochloride with alkali, is a viscous liquid of pale yellow colourboiling at 189l91 C./ 0.1 mm. Hg.

Analysis for C H O N (percent). Calc.: C, 77.64; H 7.49; N, 4.53. Found:C, 77.95; H, 7.53; N, 4.49.

The following compounds are prepared in an analogous manner:

Z-dimethylaminoethyl ;3-( l-naphthyl) -acrylate B.P. 170-175 C./0.2 mm.Hg.

Analysis for C1'1H1902N (percent). Calc.: C, 75.81; H, 7.11; N, 5.20.Found: C, 76.3; H, 7.10; N, 5.39. Hydrochloride: M. Pt. 153 C.

2- (N-pyrrolidino -ethyl fl-( 1-naphthyl)-acrylate B.P. 197-199 C./mm.Hg.

Analysis for C H O N (percent). Calc.: C, 77.26; H, 7.17; N, 4.74.Found: C, 77.50; H, 7.18; N, 4.88. Hydrochloride: M.P. 151 C.

1-phenyl-2-dimethylaminoethyl /8-( 1-naphthy1)-acrylate M.P. 82-83 C.(crystallized from isopropanol. Analysis for C H O N (percent). Calc.:C, 79.97; H, 6.71; N, 4.06. Found: C, 79.83; H, 6.82; N, 4.00.Hydrochloride: M.P.181-183 C.

l-phenyl-Z- (N-morpholino) -ethyl [3-( 1-naphthyl)- acrylate M.P. 117 C.(crystallized from 95% ethanol). Analysis for C H O N (percent). Calc.:C, 77.49; H, 6.50; N, 3.62. Found: C, 78.00; H, 6.59; N, 3.61.Hydrochloride: M.P. ZOO-204 C.

1-phenyl-2- (N-piperidino) -ethy1 fi- 1-naphthyl)- acrylate M.P. 78-79C. (crystallized from 95% ethanol). Analysis for CzeHzqOzN (percent).Calc.: C, 81.01; H, 7.06; N, 3.63. Found: C, 81.46; H, 7.11; N, 3.67.Hydrochloride: M.P. 191192 C.

EXAMPLE 2 A suspension of 50 g. of sodium fi-(l-naphthyD-acrylate and33.9 g. of 2-(N-morpholino)-1-chloroethane in 400 ml. of isopropanol isrefluxed for 20 hours. The sodium chloride, formed during the reaction,is then filtered off in the warm. The crude 2-(N-morpholino)-ethyl fl-(1-naphthyl)-acrylate crystallizes upon cooling and, afterrecrystallisation from isopropanol, melts at 80-82 C.

Analysis for C H O N (percent). Calc.: C, 73.29; H, 6.80; N, 4.50.Found: C, 73.01; H, 6.81; N, 4.60. Hydrochloride: M.P. 213 C.

EXAMPLE 3 11 ml. of a 18% solution of methyl bromide in benzene areadded to 4.1 g. of 2-dimethylaminoethyl fl-(l-naphthyl)-acrylate in ml.of anhydrous benzene and the mixture is maintained at room temperaturefor 2 days. The precipitate thus formed is separated by filtration,Washed with benzene and then With ether. Z-dimethylaminoethylfl-(l-naphthyD-acrylate methyl bromide is thus obtained as a whitecrystalline solid melting at 174 C.

Analysis for C H O NBr (percent). Calc.: C, 59.35; H, 6.08; N, 3.84; Br,21.94. Found: C, 60.12; H, 6.10; N, 3.91; Br, 22.05.

The following quaternary salts are prepared in an analogous manner:

2-dimethylaminoethyl B-( 1-naphthyl)-acry1ate n.butyl bromide Reactiontime: 4 days, M.P. 186188 C. Analysis for C H O NBr (percent). Calc.: C,62.06; H, 6.94; N, 3.45; Br, 19.66. Found: C, 62.36; H, 7.01; N, 3.39;Br, 1915.

Z-dimethylaminoethyl fi- 1-naphthyl)-acrylate isomayl bromide Reactiontime: 5 days, M.P. 182186 C. Analysis for C H O NB1" (percent). Calc.:C, 62.87; H, 7.19; N, 3.33; Br, 19.01. Found: c, 62.01; H, 7.00; N,3.31; Br, 19.11.

6 Z-dimethylaminoethyl ,B-( 1-naphthy1)-acrylate 6-bromohexyl bromideReaction time: 7 days, M.P. 189190 C. Analysis for C H O NBr (percent)Calc.: C, 53.8; H, 6.09; N, 2.73; Br, 31.14. Found: C, 53.91; H, 6.11;N, 2.69; Br, 31.01.

2-dimethylaminoethyl fil-naphthyl) -acrylate n-octyl bromide Reactiontime: 7 days, M.P. 157158 C. Analysis for C H O NBr (percent). Calc. C,64.93; H, 7.85; N, 3.03; Br, 17.28. Found: C, 64.95; H, 7.77; N, 3.03;Br, 17.41.

Z-dimethylaminoethyl ,B-( 1-naphthyl-) acrylate n-decyl bromide Reactiontime: 12 days, M.P. -168 C. Analysis for C H O NBr (percent). Calc.: C,66.10; H, 8.22; N, 2.86; Br, 16.29; Found: C, 66.01; H, 8.19; N, 2.89;Br, 16.33.

Z-dimethylaminoethyl fl- 1-naphthyl)-acrylate n-dodecyl bromide Reactiontime: 12 days, M.P. 156-15 8 C. Analysis for C H O NBr (percent). Calc.:C, 67.20; H, 8.55; N, 2.70; Br, 15.41. Found: C, 67.41; H, 8.56; N,2.69; Br, 15.45.

2- (N-morpholino -ethyl ,3-( l-naphthyl) -acrylate methyl bromideReaction time: 3 days, M.P. -177 C. Analysis for C H O NBr (percent).Calc. C, 59.12; H, 5.95; N, 3.45; Br, 19.67. Found: C, 59.91; H, 5.88;N, 3.43; Br, 19.66.

2-(N-piperidino)-ethyl fi- 1-naphthyl)-acrylate methyl bromide Reactiontime: 2 days, M.P. 175 C. Analysis for C H O NBr (percent). Calc.: C,62.38; H, 6.48; N, 3.46; Br, 19.77. Found: C, 62.43; H, 6.43; N, 3.51;Br, 19.60.

2-(N-pyrrolidino)-ethyl fi-( 1-naphthyl)-acrylate methyl bromideReaction time: 2 days, M.P. 178 C. Analysis for C H O NBr (percent).Calc.: C, 61.54; H, 6.20; N, 3.59; Br, 20.47. Found: C, 61.10; H, 6.18;N, 3.51; Br, 20.39.

2- N-pyrrolidino -ethyl B- l-naphthyl) -acrylate n-butyl bromideReaction time: 6 days, M.P. 214220 C. Analysis for C H O NBr (percent).Calc.: C, 63.90; H, 6.99; N, 3.24; Br, 18.48. Found: C, 63.10; H, 6.88;N, 3.21; Br, 18.53.

2- (N-pyrrolidino -ethyl fl-( l-naphthyl) -acrylate isoamyl bromideReaction time: 6 days, M.P. 2132l8 C. Analysis for C H O NBr (percent).Calc.: C, 64.56; H, 7.23; N, 3.14; Br, 17.90. Found: C, 64.59; H, 7.21;N, 3.11; Br, 17.50.

2- N-pyrrolidino) ethyl ,8-( 1-naphthyl)-acrylate 6-bromohexyl bromideReaction time: 7 days, M.P. 80100 C. Analysis for C H O NBr (percent).Calc.: C, 55.60; H, 6.16; N, 2.59; Br, 29.63. Found: C, 55.99; H, 6.11;N, 2.58; Br, 29.50.

2- (N-pyrrolidino -ethyl ,8-( l-naphthyl -acrylate n.0cty1 bromideReaction time: 8 days, M.P. 132133 C. Analysis for C27H33O2NBr(percent). Calc.: C, 66.38; H, 7.84; N, 2.87; Br, 16.36. Found: C,66.55; H, 7.81; N, 2.90; Br, 16.41.

1-penyl-2-dimethylaminoethyl fi-( 1-naphthyl)- acrylate methyl bromideReaction time: 2 days, M.P. 218 C. Analysis for C H O NB1' (percent)Calc.: C, 65.48; H, 5.95 N, 3.18; Br, 18.15. Found: C, 65.91; H, 5.88;N, 3.18; Br, 18.67.

7 1-pheny1-2-dimethylaminoethyl ,B-( 1-naphthyl)- acrylatedimethylsulphate Reaction time: 14 days, M.P. 168-172 C. Analysis for CH O NS (percent). Calc.: C, 63.68; H, 6.20; N, 2.97. Found: C, 62.9; H,6.21; N, 2.84.

1-phenyl-2-dimethylarninoethyl /3-( 1 -naphthyl acrylate methyl iodideReaction time: 2 days, M.P. 173-176 C. Analysis for C H O NI (percent).Calc.: C, 59.12; H, 5.38; N, 2.87; I, 26.06. Found: C, 59.90; H, 5.29;N, 2.89; I, 26.19.

1-phenyl-2-dimethylaminoethyl ,B-(I-naphthyD- acrylate n-butyl bromideReaction time: 20 days, M.P. 160-165 C. Analysis for CzqHgzOgNBI'(percent). Calc.: C, 67.20; H, 6.69; N, 2.91; Br, 16.57. Found: C,67.44; H, 6.55; N, 3.01; Br, 16.66.

1-phenyl-2-dirnethylaminoethyl ,8-( 1-n aphthyl acrylate isoamyl bromideReaction time: 20 days at 50 C. The product was isolated by removal ofthe solvent. M.P. 84-88 C. Analysis for C H O NBr (percent). Calc.: C,67.73; H, 6.90; N, 2.82; Br, 16.10. Found: C, 67.91; H, 6.83; N, 2.86;Br, 16.44.

1pheny1-2-dimethylaminoethyl B- 1-naphthyl)-acrylate 6-bromohexylbromide Reaction time: 7 days, M.P. 70-75 C. Analysis for C H O NBr(percent). Calc.: C, 59.12; H, 5.99; N, 2.38; Br, 27.11. Found: C,59.01; H, 6.03; N, 2.18; Br, 27.03.

1-phenyl-2-dimethylaminoethyl fl-( 1-naphthyl)-acrylate n-octyl bromideReaction time: 8 days, M.P. 82 C. Analysis for C H O NB1 (percent).Calc.: C, 69.13; H, 7.49; N, 2.60; Br, 14.84. Found: C, 69.51; H, 7.57;N, 2.59; Br, 14.99.

1-pheny1-2-dimethylaminoethyl fi-( 1-naphthyl)-acrylate n-decyl bromideReaction time: 20 days, M.P. 74-78 C. Analysis for C H O NBr (percent).Calc.: C, 70.00; H, 7.82; N, 2.47; Br, 14.10. Found: C, 70.61; H, 7.94;N, 2.47; Br, 14.14.

1-phenyl-2-dimethylaminoethyl B-( 1-naphthyl)-acrylate n-dodecyl bromideReaction time: 25 days, M.P. 98-102 C. Analysis for C H O NB1"(percent). Calc.: C, 70.7; H, 8.14; N, 2.36; Br, 13.44. Found. C, 70.8;H, 8.11; N, 2.40; Br, 13.39.

1-phenyl-2 N-morpholino -ethyl ,8-(1-naphthyl)- acrylate methyl bromideI-phenyl-Z-(N-piperidino)-ethyl ,8-( 1-naphthyl)- acrylate methylbromide Reaction time: 8 days, M.P. 212 C. Analysis for C27H3 O NBr(percent). Calc.: C, 67.50; H, 6.29; N, 2.91; Br, 16.63. Found: C,67.39; H, 6.27; N, 2.70; Br, 16.91.

l-phenyl-Z-(N-piperidino)-ethyl B-(l-naphthyD-acrylate acetyl chlorideReaction time: 2 days, M.P. 193-194" C. Analysis for C H O NCI(percent). Calc.: C, 72.50; H, 6.52; N, 3.02; Cl, 7.64. Found: C, 72.81;H, 6.39; N, 3.18; Cl, 7.80.

EXAMPLE 4 3.62 g. of hexadecyl bromide are added, at 50 C., to 2.9 g. ofZ-dimethylaminoethyl -(1-naphthyl)-acrylate dissolved in a mixture ofml. of anhydrous acetonitrile and 10 ml. of anhydrous benzene and thesolution thus obtained is maintained at 50 C. for 20 days. The solidthus formed is separated by filtration and then Washed first withbenzene and then with ether. The 2- dirnethylaminoethyl,8(1-naphthyl)-acrylate hexadecyl bromide is thus obtained as a Whitecrystalline solid melting at 157-160 C.

Analysis for C H O NBr (percent). Calc.: C, 69.00; H, 9.12; N, 2.44; Br,13.91. Found: C, 69.21; H, 9.10; N, 2.39; Br. 14.06.

The following quaternary ammonium salts are obtained in an analogousmanner:

2-(N-morpholino)-ethyl B-(l-naphthyD-acrylate n-butyl bromide Reactiontime: 5 days. The compound was isolated by removal of the solvent. M.P.177-187 C. Analysis for C H O NBr (percent). Calc.: C, 61.6; H, 6.74; N,8.12; Br, 17.82. Found: C, 62.0; H, 6.77; N, 3.21; Br, 17.91.

2-(N-morpholino)-ethyl B-(l-naphthyD-acrylate n-octyl bromide Reactiontime: 20 days, M.P. 86-88" C. Analysis for C27H3303NBr (percent). Calc.:C, 64.28; H, 7.59; N, 2.78; Br, 15.84. Found: C, 65.00; H, 7.61; N,2.70; Br. 15.89.

2- Nmorpholino) ethyl fi-( 1-naphthyl)-acrylate n-decyl bromide Reactiontime: 60 days. The product was isolated by removal of the solvent. M.P.88-92 C. Analysis for C H O NBr (percent). Calc.: C, 65.40; H, 7.95; N,2.63; Br, 15.01. Found: C, 65.10; H, 7.88; N, 2.67; Br, 15.15.

Z-(N-morpholino -et-hyl fl-( 1-naphthyl)-acrylate n-dodecyl bromideReaction time: 60 days. The product was isolated by removal of thesolvent. M.P. 7680 C. Analysis for C H O NBr (percent). Calc.: C, 66.40;H, 8.27; N, 2.50; Br, 14.26. Found: C, 66.93; H, 8.31; N, 2.50; Br,14.38.

2- N-piperidino -ethyl [i-(1-naphthy1)-acrylate n-octyl bromide Reactiontime: 8 days, M.P. -157 C. Analysis for C H O NB1 (percent). Calc.: C,66.92; H, 8.02; N, 2.79; Br, 15.90. Found: C, 66.18; H, 8.01; N, 2.81;Br, 15.66.

2-(N-pyrro1idino)-ethyl /3-(1-naphthyl)-acrylate n-decyl bromideReaction time: 20 days, M.P. 92.95 C. Analysis for C H O NBr (percent).Calc.: C, 67.45; H, 8.20; N, 2.71; Br, 15.47. Found: C, 67.91; H, 8.19;N, 2.83; Br, 15.41.

2- (N-pyrro1idino)-ethyl 3-(1-naphthyl)-acrylate n-dodecyl bromideReaction time: 25 days, M.P. 90-95 C. Analysis for C H O NBr (percent).Calc.: C, 68.40; H, 8.52; N, 2.57; Br, 14.67. Found: C, 68.10; H, 8.55;N, 2.59; Br, 14.55.

2- N-pyrrolidino -ethyl 18- 1-naphthyl)-acrylate n-octadecyl bromideReaction time: 25 days, M.P. 82-86 C. Analysis for C37H5302NBI'(percent). Calc.: C, 70.68; H, 9.30; N, 2.23; Br, 12.71. Found: C,70.00; H, 9.19; N, 2.18; Br, 12.75.

1-phenyl-Z-dimethylaminoethyl ,8-(1-naphthyl)-acrylate n-octadecylbromide Reaction time: 45 days. The compound was isolated by removal ofthe solvent. M.P. 8286 C. Analysis for 9 C H O NBr (percent). Calc.: C,72.52; H, 8.92; N, 2.06; Br. 11.77. Found: C, 72.80; H, 8.99; N, 2.15;Br, 11.51.

1-phenyl-2- (N-piperidino) -ethy1 B-( l-naphthyl) -aorylate n-octyliodide Reaction time: 20 days. The product was isolated by removal ofthe solvent. M.P. 158-163 C. Analysis for C H O NI (percent). Calc.: C,65.28; H, 7.09; N, 2.24; I, 20.29. Found: C, 65.53; H, 7.12; N, 2.25; I,20.23.

1-pheny1-2- (N-piperidino) -ethyl B-( 1-naphthy1)-acry1ate n-decylbromide Reaction time: 20 days, M.P. 168-171 C. Analysis for C H O NBr(percent) Calc.: C, 71.30; H, 7.98; N, 2.31; Br, 13.17. Found: C, 71.48;H, 8.05; N, 2.47; Br, 13.21.

EXAMPLE 1.28 g. of benzyl chloride are added to a solution of 2.87 g. of2-dimethylaminoethyl fi-(l-naphthyD-acrylate in 5 ml. of anhydrousacetone and the solution maintained at room temperature for 2 days. Thesolid which thus separates is separated by filtration and Washed withether.

The Z-dimethylaminoethyl fi-(l-naphthyD-acrylate benzyl chloride is thusobtained as a white crystalline solid melting at 197198 C.

Analysis for C H O NCI (percent). Calc.: C, 72.80; H, 6.62; N, 3.55; Cl,8.95. Found: C, 72.51; H, 6.60; N, 3.57; Cl, 9.01.

The following quaternary ammonium salts are obtained in an analogousmanner:

2- (N-morpholino -ethyl ,8-( 1-naphthyl)-acrylate benzyl chlorideReaction time; reaction temperature: 5 days at 50 C. M.P. 166167 C.Analysis for C H O NCl (percent). Calc.: C, 71.30; H, 6.44; N, 3.20; Cl,8.09. Found: C, 70.99; H, 6.43; N, 312; Cl, 8.13.

2-(N-piperidino)-ethyl /3-( l-naphthyl) -acrylate benzyl chlorideReaction time: 5 days, M.P. 189191 C. Analysis for C27H3002NC].(percent). Calc.: C, 74.38; H, 6.94; N, 3.21; Cl, 8.13. Found: C, 74.42;H, 6.99; N, 3.19; Cl, 8.16.

2-(N-pyrrolidino)-ethyl fl-(l-naphthyD-acrylat benzyl chloride Reactiontime: 5 days, M.P. 176 C. Analysis for C H O NCl (percent). Calc.: C,74.01; H, 6.69; N, 3.32; CI, 8.40. Found: C, 74.62; H, 6.83; N, 3.31;Cl, 8.39.

1-phenyl-2-dimethylaminoethyl ;8-( 1-naphthy1)-acrylate benzyl bromideReaction time: 15 days. Reaction temperature: 50 C. The compound wasisolated by removal of the solvent. M.P. 60-65 C. Analysis for C H O NBr(percent). Calc.: C, 69.75; H, 5.85; N, 2.71; Br, 15.47. Found: C,69.95, H, 5.72; N, 2.58; Br, 15.39.

1-phenyl-2-dimethylaminoethyl 18- 1-naphthy1)-acrylate benzyl chlorideReaction time: 20 days, M.P. 178181 C. Analysis for C H O NCl (percent).Calc.: C, 76.34; H, 6.41; N, 2.97; Cl, 7.51. Found: C, 76.34; H, 6.31;N, 2.79; Cl, 7.61.

1-phenyl-2- (N-piperidino -ethyl ;8-( 1-naphthyl)-acrylate benzylchloride Reaction time: 20 days. Reaction temperature: 50 C., M.P. 1051C. Analysis for C H O NCl (percent). Calc.: C, 77.40; H, 6.69; N, 2.73;Cl, 692. Found: C, 77.10; H, 6.80; N, 2.75; Cl, 6.84.

10 EXAMPLE 6.--TINCTURES n-decyl bromide g 0.5 5 70% alcohol, q.s. to ml100 (b) 2- (-N-pyrrolidino) -ethyl fl- 1-naphthyl)-acrylate n-decylbromide 'g 1 Industrial methylated spirits ml 75 Distilled water, q.s.to ml 100 10 EXAMPLE 7.-AQUEOUS SOLUTIONS (a) For pro-operative skindisinfectant:

2- (-N-pyrrolidino -ethyl 3- l-naphthyl -acryla n-decyl bromide -g 1Propylene glycol ml 5 Distilled water, q.s. to ml 100 (b) Disinfectantfor the hands and arms of the surgeon before sungical procedures: A B 2-(N pyrrolidino) -ethyl ,8- 1-naphthyl acrylate n-decyl bromide g 0.5 0.1Propylene glycol ml 5 5 'Distilled water, q.s. to ml 100 100 (c)Disinfectants for use in obstetrics and for burns and wounds:

2- (N pyrrolidino) -ethyl B- 1-naphthyl -acrylate n-decyl bromide g 0.05Propropylene lglycol ml 5 Distilled water, q.s. to ml 100 EXAMPLE8.-CREAMS Grams (a) 2-(N-pyrrolidino)-ethyl fl-(l-naphthyD- ecrylaten-decyl bromide 0. 5 0. 1 Cetostearyl alcohol. 10 10 Liquid parafiin 1010 Distilled water, q.s. t 100 100 (b) 2-(N-pyrrolidino)-ethyl 40acrylate n-decyl bromide 0. 5 0. 1 Polyethylene 1000 monocetyl ether. 22 Cetostearyl cohol 8 8 Cetyl alcohol 5 5 Yellow soft parafiin 10 10Liquid paraflin 10 10 Glycerin 5 5 Distilled water, q.s. to 100 100EXAMPLE 9.-LOTIONS Grams 2-(N-pyrrolidino) ethyl B-(l-naphthyD-acrylaten-decyl bromide 0. 5 0. 1 01 3 3 2 2 20 20 2 2 100 100 EXAMPLE10.VAGINAL TABLETS Grams Each tablet contains:

2-(N-pyrrolidino)-ethyl fl-(l-naphthybacrylate n-decyl bromide 0. 005 00005 Polysorbate 80 0. 010 0 010 Lactose, q.s. to 2 EXAMPLE 11.-VAGI'NALSUPPOSITOR-IES Grams Each suppository contains:

2-(N-pyrrolidino)-ethyl B-(l-naphthyD- acrylate n-decyl bromide 0. 0050. 0005 Glycerinated gelatine, q.s. to 2 2 EXAMPLE 12.LOZENGES GramsEach lozenge contains:

acrylate n-decyl bromide. 0. 002 0. 0005 Mannitol 0. 200 0.200

Talc 0.020 0.020

Flavour, q.s

Sugar, q.s. to 1 1 EXAMPLE 13.EAR DROPS 2-(N-pyrrolidino)-ethylfl-(l-naphthyl) -aeryla-te ndeeyl bromide, g 0. 0. 02

Propylene glycol (ml.), q.s. to 100 100 I claim:

1. A compound of the formula wherein R is selected from the groupconsisting of a hydrogen atom and a phenyl group; R and R takenindividually represent a group selected from the group consisting ofmethyl and ethyl, or when taken collectively with the nitrogen atom towhich they are attached represent a heterocycle selected from the groupconsisting of piperidino, morpholino and pyrrolidino; R is selectedReferences Cited UNITED STATES PATENTS 2,415,079 2/1947 Blicke 260-4693,077,470 2/1963 Burckhalter 260239 FOREIGN PATENTS 581,532 8/1959Canada.

OTHER REFERENCES Chemical Abstracts, vol. 46, col. 11168 (1952)(abstract of Sergievskaya et a1.)

Chemical Abstracts, vol. 65, cols. 1752 to 1754 (1965) (abstract ofCrescenzi et a1.)

Chemical Abstracts, vol. 65, col. 2135 (1965 (abstract of Coppi et 211.)

JOHN D. RANDOLPH, Primary Examiner.

US. Cl. X.R. 260469; 424308, 274, 267, 248

